Irena Alexandra Rebalka

This study demonstrates that adipocyte ATGL is a critical regulator of adipose-muscle metabolic crosstalk. Limiting adipocyte lipolysis through adipose ATGL deletion reduced blood lipid and ketone fuel availability, thereby increasing adipose retention, decreasing skeletal muscle mass and fiber size, and increasing muscle atrogene expression, particularly during intermittent fasting. These findings support a model in which impaired adipocyte lipid mobilization shifts whole body energy demands away from adipose and toward skeletal muscle, promoting muscle catabolism during fasting.

Axiobasilaris is an accessory muscle of the prevertebral region. While historical cases have been described in the late 19th century, to our knowledge, no new reports of this muscular variation have been published since that time period. Visual representation of axiobasilaris is also lacking aside from illustrations produced in 1880 by Gruber. Recording anatomical variations is valuable for both teaching and clinical practice, as variations may be encountered by anatomists in the dissection laboratory and cause implications in the surgical setting. Prevertebral variations such as axiobasilaris are relevant in cases of endoscopic endonasal skull base surgery, trans-oral release and reduction of the cervical spine, as well as cervical corpectomy. From a functional perspective, axiobasilaris is thought to contribute to flexion at the atlanto-occipital and atlanto-axial joints. This study aims to determine the prevalence of axiobasilaris through the dissection of 60 donor cadavers (120 sides). Axiobasilaris was found in five out of the 60 (8.33%) donors dissected in this study; two cases presented as a single unilateral muscle, while three others presented as paired bilateral muscles for a total of eight out of 120 sides (6.67%).

Statin intolerance and side effects such as low-level myopathy limit statin use and the dose for optimal cholesterol lowering. We found that priming the NLRP3 inflammasome with bacterial components like lipopolysaccharide lowered the dose of statins that caused side effects in muscle cells. We then built models of low-level statin myopathy and found that muscle cell–autonomous statin-induced myopathy occurs through the NLRP3 inflammasome in vitro and in mice. Statin-induced muscle cell death and higher Atrogin-1 were prevented by blocking NLRP3 or restoring isoprenoids but not cholesterol. Statins reduced glycolysis in muscle cells, which required lower protein prenylation. Statins lowered YAP effector genes and promoted nuclear accumulation of FOXO. Activating YAP, restoring isoprenoids, or blocking NLRP3 mitigated nuclear FOXO accumulation, statin-induced muscle atrophy, and statin-mediated lowering of protein synthesis. These results define a statin-induced myopathy pathway where metabolic danger engages the NLRP3 inflammasome and YAP via lower prenylation independent of cholesterol.

While older adults are the most prominent human cohort currently necessitating or receiving cholesterol-lowering statin therapy, most preclinical testing of the efficacy and side effects that accompany statin use are conducted on juvenile adult rodents. Furthermore, varying pharmacodynamics between hydrophilic and lipophilic statins may lead to different therapeutic outcomes. The purpose of this study was to compare the efficacy, specifically modifications to cardiovascular parameters, and safety, namely presence or absence of a pathological skeletal muscle phenotype, of hydrophilic rosuvastatin (RSV) versus lipophilic atorvastatin (ATV) therapy in a geriatric rodent model. Briefly, 25- to 27-month-old Wistar rats were provided control, RSV, or ATV treatment for 30 days. Cardiac hemodynamics, muscle functional testing, open-field behaviours, and skeletal muscle morphology were evaluated. Whole-heart weight was lower in ATV-treated than in RSV-treated animals. Heart rate, rate of left ventricle pressure change, and arterial pressure were lowered by ATV but not RSV. These results are hypothesized to suggest attenuation of age-related sympathetic overactivity with ATV treatment. No differences in muscle histology, function, or open-field testing behaviours were observed between groups, indicating the absence of an overt statin-associated skeletal muscle phenotype. Overall, in geriatric rodents that more appropriately mimic the age of humans that are prescribed statin therapy, lipophilic ATV, but not hydrophilic RSV, had positive effects on cardiac function without negatively impacting the skeletal muscle.

This study demonstrates significantly perturbed amino acid pools within muscle as a result of tumor growth, with marginal additive effects of doxorubicin administration. Notably, tumor amino acid pools remain primarily unchanged despite muscle suggesting significant changes, which may be indicative of structural damage or reduced ability to produce energy.

Anatomy education is an inherently visual field, particularly in bellringer (BR) testing, which requires learners to identify anatomical structures on human‐donated specimens. While the traditional use of these physical specimens in BR testing has long remained the standard, three‐dimensional (3D) viewing in virtual reality platforms and two‐dimensional (2D) images of specimens on paper have become common alternatives due to the ease and feasibility of use. Despite widespread use, there is a paucity of literature comparing the assessment validity of these modalities to physical specimens as the historic standard. Thus, this study sought to assess BR testing performance and question validity (using point biserial evaluation) across all three modalities. In total, 140 undergraduate students, enrolled in an Introductory Anatomy and Physiology course at the time of testing, participated in a BR examination with specimens presented in three visual formats: physical specimens, printed 2D images, and 3D reconstructions in virtual reality. When comparing all three modalities, no notable differences were found between question difficulty, point biserial values, presentation of cybersickness, visuospatial ability, or modality preference. Additionally, modality preference and student opinion did not significantly affect test scores, suggesting that these student attributes were unrelated to BR performance. The examinations had high reliability as measured by KR‐20 values, supporting the applicability of our results to undergraduate anatomy BR testing. This study provides preliminary evidence supporting the utility and validity of both 2D images and 3D virtual reality as alternative modalities for BR testing within the undergraduate anatomy education setting.

Doxorubicin is a commonly used chemotherapy that rapidly accumulates in skeletal muscle and disrupts nitric oxide (NO) formation. However, studies investigating these effects have largely been performed in tumour-free models, therefore it remains unknown whether intramuscular accumulation and disruptions to NO content persist during tumour growth. Female C57bl/6 mice ( n = 8/group) were randomly assigned to true control, doxorubicin control, tumour only, or tumour plus doxorubicin groups. Tumours were grown for 21, 24, or 28 days using E0771 cells. Doxorubicin was administered as a single 10 mg/kg intraperitoneal dose on day 21. Doxorubicin accumulation was similar in muscle with and without tumours present. Doxorubicinol, a metabolite of doxorubicin, was elevated ( p < 0.05) in 24-day tumour + doxorubicin compared to doxorubicin alone. NO was similar across all groups in muscle; however, tumour NO was 15-fold higher at day 21 compared to 24, or 28 days ( p < 0.05). The results confirm that doxorubicin is sequestered in skeletal muscle when a tumour is present, which may impact bioavailability. Tumour growth transiently increased intramuscular doxorubicinol, potentially exacerbating the toxicity of the drug. Earlier stage tumour growth appeared to profoundly elevate NO, which could suggest temporal angiogenesis and vasodilation to facilitate growth.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and weakness. Prescribed moderate exercise in patients is beneficial, but concerns remain due to the vulnerability of dystrophic muscle to damage. Voluntary wheel running (VWR) is a self‐regulated form of exercise that improves muscle health in the typical C57.mdx mouse model of DMD. The purpose of the current study was to investigate the impact of VWR in more severe and clinically relevant D2.mdx mice. Male D2.mdx animals were assigned to a sedentary (D2.mdx SED) or VWR group for 8–10 weeks, whereas DBA/2J wild‐type mice served as healthy, sedentary controls (WT SED). Selective skeletal muscle mass and ex vivo force generation were elevated in D2.mdx animals that ran a relatively high volume (D2.mdx High VWR; 1.84 ± 0.84 km/day) compared to low‐volume runners (D2.mdx Low VWR; 0.46 ± 0.31 km/day) and SED counterparts. VWR did not exacerbate the dystrophy, and instead attenuated the fibrotic profile compared to D2.mdx SED mice. A VWR‐induced shift towards a more slow, oxidative phenotype was also observed. Mitochondrial respiration was reduced in D2.mdx SED animals versus WT SED mice but was partially restored following both Low and High VWR. Finally, a dose‐dependent increase in the expression of mitochondrial proteins was observed following VWR, whereas markers of mitochondrial fusion were particularly elevated in D2.mdx High VWR mice. Our results indicate that VWR enhances muscle and mitochondrial biology in D2.mdx animals and further supports the therapeutic role of exercise for DMD patients. image Key points: Duchenne muscular dystrophy (DMD) is a life‐limiting neuromuscular disorder characterized by muscle weakness and wasting. Skeletal and cardiac muscle quality is compromised in the dystrophic condition. Exercise promotes functional and molecular adaptations in healthy individuals and mild dystrophic mouse models. However, the effects of exercise in more severe and clinically relevant models of DMD require investigation. A relatively high volume of voluntary wheel running (VWR) augmented selective muscle mass and muscle function without exacerbating the dystrophic pathology in D2.mdx mice. Volitional exercise normalized dystrophic skeletal muscle mitochondrial respiration and upregulated mitochondrial content compared to sedentary counterparts. A higher dose of VWR increased organelle fusion protein expression compared to both healthy and dystrophic sedentary animals, as well as D2.mdx mice that ran lower volumes. Our results provide evidence from a severe preclinical model that volitional exercise may be a safe and efficacious lifestyle‐based intervention for DMD.

With increasing evidence that ketogenic diets improve aspects of muscle health (e.g., insulin sensitivity and mitochondrial function), we hypothesized that supplementation with GABA—a key metabolite changed with ketogenic diets—would improve muscle recovery from injury. Unexpectedly, GABA supplementation during the early inflammatory phases of muscle regeneration delayed muscle repair in type 1 diabetes mice, possibly due to inflammation suppression. Further work is needed to ascertain the effective use of GABA supplementation, particularly following intense or damaging exercise.